# BOOST:Better Oncology Outcomes Through Statin Treatment

> **NIH VA IK2** · PORTLAND VA MEDICAL CENTER · 2024 · —

## Abstract

Background: Melanoma is an aggressive skin cancer and the fifth most common cancer in the US population.
Most melanomas are diagnosed at an early, localized stage, but approximately 10-15% of these melanomas
eventually metastasize despite appropriate treatment. This progression of localized melanoma to metastatic
disease is a leading cause of morbidity and mortality. In addition, the cost of treating metastatic disease has
risen rapidly over the past decade. No treatment exists for melanoma patients who are at high risk of future
metastasis, but whose clinical stage does not qualify for existing adjuvant treatments. Thus, there is a clear
need for treatments that would decrease metastasis while being tolerable and cost-effective.
Significance: This proposal uses VA specific datasets (Corporate Data Warehouse, Million Veteran Program)
to evaluate the efficacy of statins as a treatment to reduce melanoma metastasis and mortality. Multiple
orthogonal approaches are proposed in order to generate robust data that will serve as a foundation for a
future clinical trial of statins in the prevention of melanoma metastasis.
Innovation: This proposal is based on an innovative approach to drug discovery for high-risk melanoma.
Statins were identified as a promising treatment candidate based on gene expression profiling. This proposal
will use advanced statistical methods in order to assess the correlation of statin use with melanoma metastasis
and mortality rates in the Veteran population and create the foundation for a future clinical trial. In addition, this
proposal will use Mendelian randomization paired with germline genetic data from the Million Veteran Program
(MVP) in order to assess potential causal effects between HMGCR enzyme function and melanoma
metastasis.
Specific Aims: 1) Determine whether distant metastasis free survival (DMFS) is associated with incident statin
use in a retrospective Veteran cohort. 2) Determine which statin-intrinsic properties correlate most strongly with
melanoma mortality. 3) Evaluate the effect of common variants in the HMGCR gene on overall and metastasis-
free survival in patients with melanoma using germline genetic data from the Million Veterans Program (MVP).
Methods: Aim 1 will use data extracted from the VA Corporate Data Warehouse to assess the association of
incident statin use on melanoma distant metastasis free survival. Aim 2 dissects the effects of the mevalonate
pathway on melanoma metastasis by comparing statins to downstream inhibitors. In addition, Aim 2 evaluates
the relative correlation of dose and statin intensity on melanoma mortality. Aim 3 uses Mendelian
randomization (MR), a biostatistical technique, to assess the relationship between HMGCR variants and
melanoma mortality. MR mimics a randomized clinical trial, and thus, data generated by this Aim would
potentially support a causative relationship between HMGCR protein function and melanoma metastasis.
Taken together, this proposal may support a...

## Key facts

- **NIH application ID:** 10806018
- **Project number:** 1IK2CX002642-01A1
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** Wesley Y Yu
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806018

## Citation

> US National Institutes of Health, RePORTER application 10806018, BOOST:Better Oncology Outcomes Through Statin Treatment (1IK2CX002642-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10806018. Licensed CC0.

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